Dr. Yi-Ping Li
The University of Texas Health Science Center at Houston
Department of Integrative Biology and Pharmacology
Striated muscles (skeletal and cardiac muscle) undergo remodeling, either positive or negative, in response to physiological and pathological stress. For example, many inflammatory diseases including cancer, AIDS, sepsis, diabetes, and congestive heart failure induce debilitating muscle atrophy or wasting due to loss of muscle mass (cachexia). On the other hand, diseased or injured muscle has the capacity to regenerate leading to recovery of muscle mass and function. In addition, cardiac muscle chronically exposed to high blood pressure develops hypertrophy and eventually left ventricle dilation (congestive heart failure). The research in my lab is aimed at dissecting the signaling mechanisms that regulate the remodeling processes using molecular and cellular approaches, and testing therapeutic strategies using in vitro and in vivo models. We are currently working on three projects:
Mechanism of skeletal muscle wasting: Our lab is interested in the role of inflammatory mediators in mediating accelerated muscle protein degradation associated with many chronic diseases. We investigate the signaling mechanisms of inflammatory mediator stimulation of the ubiquitin-proteasome pathway and the autophagy-lysosome pathway which are responsible for accelerated muscle wasting and try to translate the basic research into clinical interventions for human patients. The study involves transcriptional regulation of specific ubiquitin ligase genes, the signaling mechanism that induces autophagy, and evaluation of muscle protein turnover in cultured muscle cells and in animal models of muscle wasting (rodents). Various gene knockout mice are used.
Regulation of skeletal muscle regeneration: Skeletal muscle adapts to various stresses (injury, disease and training) by regenerating to make new muscle (myogenesis). Muscle regeneration is the function of muscle stem cells (also known as satellite cells) that have the capacity to proliferate, differentiate and fuse to form new muscle fibers when stimulated by regenerative cues. We are particularly interested in the epigenetic regulation of muscle gene expression in muscle stem cells that are stimulated by various regenerative cues. The study involves regulation of muscle gene expression by focal adhesion proteins, microRNAs, and autocrine release. Various gene knockout mice are used.
Signaling mechanism of cardiac muscle adaptation to mechanical stress: Cardiac muscle responds to chronic hemodynamic overloading (mechanical stress) by developing hypertrophy (adaptation) that leads to left ventricle dilation (maladaptation). We study the mechanotransduction mechanism that mediates cardiac muscle response to overloading with the purpose of identifying ways to prevent the maladaptation specifically without blocking adaptation. We are particularly interested in the signaling mechanism that activates TNF-alpha converting enzyme (TACE) in response to overloading. Site-directed mutagenesis of the TACE protein is used to study its activation and interaction with other proteins. Primary cultures of cardiomyocytes and various gene knockout or knock-in mice are used.
Program in Cell and Regulatory Biology
Office: MSE R376
Title: Associate Professor
Ph.D. - Texas Tech University Health Sciences Center - 1990